Excessive food intake and its deleterious effects on body mass are well known. Over time, excessive food intake produces a net caloric surplus that is stored in the fat of the animal. The accumulation of excess body fat has negative consequences both on the gross level, such that the overall appearance of the animal does not conform to generally accepted morphological standards, and on the metabolic level, such that the overall health prospects of the animal may be compromised, i.e., due to stress on organ systems in the case of morbid obesity and its co-morbid conditions, such as diabetes.
Nutritional approaches that are based upon restricting the caloric intake of animals are known to have positive effects on health and average body weight. However, these approaches require active intervention on the part of humans to dispense a controlled amount of food at defined intervals. Otherwise, animals given continuous access to a food source (fed “ad libitum”) will continue consumption until the onset of satiety. However, the onset of satiety in response to food consumption is usually a gradual or delayed response which will routinely lead to consumption of more than the desired caloric limit.
Most companion animal diets that are currently on the market rely on calorie control as the means to weight loss. This approach essentially relies on brute force to control weight and relies heavily on compliance from the animal's guardian to ensure that the animal gets exactly what is required and no more. In essence, a companion animal fed ad libitum on a diet that relies on calorie restriction will still gain weight.
In a review by Kamiji and Inui (Endocrine Reviews, 28(6):664-684) the authors stated that NPY is a 36-amino acid neuropeptide member of the pancreatic polypeptide (PP) family. That includes Peptide YY (PYY) and PP. NPY is the most abundant and widely distributed peptide in the central nervous system of both rodents and humans. Within the hypothalamus, NPY plays an essential role in the control of food intake and body weight. Centrally administered NPY causes robust increases in food intake and body weight and, with chronic administration, can eventually produce obesity.
The biological actions of NPY are mediated by receptors derived from three Y receptor genes leading to the Y1, Y2 and Y5 subfamilies. All three play a role in the regulation of feeding behavior. Recent studies have shown that when NPY expression in the hypothalamus was inhibited, the treated animals released 50% less NPY, gained less weight and ate less than the controls up to 50 days after treatment (Beck, B., Phil. Trans. R, Soc. B (2006) 361, 1159-1185).
The most important factor that influences the hypothalamic content of NPY is food deprivation. Chronic food restriction induces similar changes and refeeding rapidly returns the abundance of NPY in the hypothalamus to initial values. Blood glucose concentrations also influence the expression of NPY. Furthermore, decreasing leptin levels in the blood by fasting leads to an increase in NPY expression. Additionally, gene therapy that restores leptin receptor expression in a model rat leads to a significant reduction in NPY mRNA levels pointing to a link between the leptin receptor and NPY expression (Beck, B., Phil. Trans. R, Soc. B (2006) 361, 1159-1185).